This is a proposal to establish a program-project directed to the comprehensive understanding of the basic derangements of cell function which lead to mental retardation in children. The underlying approach is the application of biochemical techniques to deliniate the abnormalities responsible for retardation syndromes associated with inherited metabolic diseases by investigation of model systems ranging from patients and intact animals to isolated cells and subcellular systems. Emphasis will be placed on growth and development as important factors. The program project is composed of six individual research projects each to be directed by an experienced researcher. These include 1) Studies of perinatal brain toxicity. 2) Myelination in chick embryos. 3) Development and regulation of brain lysosomal enzymes. 4) Regulation of galactose metabolism in perfused liver. 5) Neuronal cells in tissue culture as model systems for brain dysfunction. 6) The basis of mental retardation in human cystinuria. BIBLIOGRAPHIC REFERENCES: Pleasure, D. and Kim, S.U. Enzyme markers for myelination of mouse cerebellum in vivo and in tissue culture. Brain Research 104:193-196, 1976. Glick, M.C. Glycoproteins on the surface of neuroblastoma cells. Journal Natl. Cancer Inst. 57, 653-658, 1976.